The overall objective of this research is to advance certain techniques of HPLC of biological and toxicologically important compounds in terms of a very high degree of compound resolution and new detection techniques. Packed microcapillary columns, developed in this laboratory, give certain hopes of versatility for separation of complex biological mixtures. In addition, the very low flow-rates (typically, around l microns 1/min.) are ideal for development of new detection and ancillary techniques of HPLC, but certain advantages of higher sensitivities exist here as well. A gradual progress in both column technology and related miniaturized instrumentation appears to indicate potential importance of this new separation technique in the future. For the coming year, we have several major objectives: (a) to further optimize diameter-to-particle ratio for packed microcapillary columns and extend the column studies into areas of gel permeation chromatography; (b) to continue studies with the microflame detection system; feasibility of detection of phosphinylated biological molecules with this detector will be further investigated; (c) to extend the microflame detection; and (d) to explore feasibility of the miniaturization of transport detection systems, with a particular emphasis on LC/MS and LC/FTIR combination.